Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.

Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.
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发表时间:
1994-03
期刊:
影响因子:
11.2
通讯作者:
Y. Guo;J. Ma;J. Wang;X. Che;J. Narula;M. Bigby;M. Wu;M. Sy
Y. Guo;J. Ma;J. Wang;X. Che;J. Narula;M. Bigby;M. Wu;M. Sy
中科院分区:
医学1区
文献类型:
--
作者:
Y. Guo;J. Ma;J. Wang;X. Che;J. Narula;M. Bigby;M. Wu;M. Sy

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CD 44是一种M(r)90,000表面糖蛋白,被认为参与细胞粘附和迁移。我们使用人黑色素瘤细胞系SMMU-1和SMMU-2研究了CD 44在肿瘤生长和转移中的作用。SMMU-1和SMMU-2在皮下形成肿瘤。皮下注射时的组织但只有SMMU-2转移。接受SMMU-2 s.c.发展成转移性肿瘤在体外,SMMU-2而不是SMMU-1表达高水平的造血形式的CD 44并结合荧光缀合的透明质酸。GKW. A2是一种对人CD 44具有特异性的单克隆抗体,在体外可完全抑制透明质酸与SMMU-2肿瘤细胞的结合。此外,体内注射GKW. A3抑制SMMU-2肿瘤细胞的生长和转移潜力。在皮下给药后1周静脉内施用GKW.肿瘤注射不抑制局部肿瘤发展,但抑制转移性肿瘤的形成并延长动物存活。因此,肿瘤细胞上的CD 44与其配体在体内的相互作用可能是肿瘤生长和转移所必需的。
CD44 is a M(r) 90,000 surface glycoprotein believed to be involved in cell adhesion and migration. We investigated the role of CD44 in tumor growth and metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high levels of the hematopoietic form of CD44 and binds fluorescence-conjugated hyaluronic acid in vitro. GKW.A2 is a monoclonal antibody specific for human CD44 that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week after s.c. tumor injection did not inhibit local tumor development but inhibited the formation of metastatic tumors and prolonged animal survival. Therefore, interactions between CD44 on tumor cells and its ligands in vivo may be necessary for tumor growth and metastasis.